IL-8 induces a transient arrest of rolling eosinophils on human endothelial cells

Eosinophils exhibit a rolling interaction with E-selectin-expressing endoth elium, and need to be activated by inflammatory mediators to firmly adhere to this surface. This study shows that IL-8 induces a transient arrest of u nprimed eosinophils that roll on E-selectin present on TNF-alpha -activated HUVEC in an in vitro flow chamber. This process was antagonized by neutral izing Abs directed against IL-8 showing the specificity of the IL-8 effect. Furthermore, blocking Abs against both alpha (4) and beta (2) integrins in hibited the IL-8-induced transient arrest while these Abs had no effect whe n they were added separately. The IL-8-induced arrest was pertussis toxin s ensitive, Studying the effect of IL-8 in more detail, we evaluated putative changes in intracellular Ca2+ concentration in eosinophils induced by IL-8 , We could show that IL-8 induces a transient rise in intracellular Ca2+ co ncentration in similar to 40% of the cells provided that the eosinophils ar e interacting with endothelial cells or fibronectin-coated surfaces. Togeth er these data show that resting eosinophils respond to IL-8 provided that t he cells adhere on physiological surfaces. The induction of a transient arr est provides a new level of chemokine-induced regulation of leukocyte adhes ion under flow conditions.